Mad-1 is the exclusive JC virus strain present in the human colon, and itstranscriptional control region has a deleted 98-base-Pair sequence in colon cancer tissues

JC virus (JCV), along with other members of the polyomavirus family, encode s a class of highly conserved proteins, T antigens, that are capable of ind ucing aneuploidy in cultured cells. We have previously isolated T-antigen D NA variants of JCV from both colon cancer tissues and the corresponding non neoplastic gastrointestinal tissues, raising new questions about the role o f JCV in the development of chromosomal instability of the colon. Based on the sequence of the transcriptional control region (TCR), JCV can be classi fied as archetype or tandem repeat variants. Among the latter, Mad-1, the p rototype virus first isolated from a patient with progressive multifocal le ukoencephalopathy, is characterized by lacking the 23- and 66-bp sequences that are present in the archetype and by duplication of a 98-bp sequence. I n this study, we evaluated differences in the TCR of JCV isolated from colo n cancer tissues and nonneoplastic epithelium. To characterize JCV variants , we first treated eight pairs of DNA samples from colon cancers and noncan cerous tissue with topoisomerase I and then amplified and cloned the JCV TC R. We obtained 285 recombinant clones from the JCV TCR, 157 from nonneoplas tic samples, and 128 from colon cancer tissues. Of these clones, 262 spanne d the length of the JCV Mad-1 TCR: 99.3% from nonneoplastic samples and 82. 8% from colon cancer tissues. In sequencing 54 clones in both directions, w e did not find archetype JCV either in the nonneoplastic tissue or in the c ancer samples. From all colon cancer tissues, 18 clones had a deletion of o ne 98-bp tandem repeat. This deleted strain was not detected in any of the nonneoplastic tissues (14 versus 0% [chi (2) = 23.6; P < 0.001]). Our study demonstrates that the only JCV strain present in the human colon is Mad-1, and the variant with a single 98-bp sequence is found exclusively in the c ancer tissues. This strain may be involved in the development of chromosoma l instability.